tert-Butyl 4-oxopiperidine-1-carboxylate → tert-Butyl 4-hydroxy-4-(2-methylphenyl)piperidine-1-carboxylate

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Reaction Steps

N-Boc-4-piperidone (Boc-29.155) (200 mg, 11.0 mmol) was dissolved in 5 ml of anhydrous ethyl ether, cooled in dry ice/acetone bath. 2-Tolylmagnesium bromide (550 μl, 2M in ethyl ether, 1.1 mmol) was added dropwise over 5 min. White precipitate was formed. After 5 h, remove the dry ice/acetone bath and rise to room temperature gradually. After 2 h, cooled in ice bath, 8 ml of saturated NH4Cl and 2 ml of H2O were added. The organic phase was separated and aqueous phase was extracted with 4×10 ml of Et2O. Combined with organic phase and washed with 8 ml of H2O and 10 ml of brine, dried over MgSO4. Concentrated and dried to obtain 361 mg of colorless oil. Separated by silica gel to obtain 4f (229.7 mg, 79% yield) as colorless oil. 1H NMR (CDCl3, 200 MHz) δ 1.47 (s, 9H), 1.93 (m, 4H), 2.60 (s, 3H), 3.27 (t, 2H, J=13.0 Hz), 3.96 (d, 2H, J=12.2 Hz), 7.15 (m, 3H), 7.35 (m, 1H).

Provenance & Evidence